Sustaining and maintaining the intricate process of spermatogenesis is liable upon hormones and growth factors acting through endocrine and paracrine pathways. The Sertoli cells (SCs) are the major somatic cells present in the seminiferous tubules and are considered to be the main regulators of spermatogenesis. As each Sertoli cell supports a specific number of germ cells, thus, the final number of Sertoli cells determines the sperm production capacity. Similarly, sex hormones are also major regulators of spermatogenesis and they can determine the proliferation of Sertoli cells. In the present review, we have critically and comprehensively discussed the role of sex hormones and some other factors that are involved in Sertoli cell proliferation, differentiation and maturation. Furthermore, we have also presented a model of Sertoli cell development based upon the recent advancement in the field of reproduction. Hence, our review article provides a general overview regarding the sex hormonal pathways governing Sertoli cell proliferation and development.
1 Adult male albino rats (CF Strain) were administered i.p. CS2 dissolved in cotton seed oil at doses of 25, 50, 100 and 200 mg/kg b.wt. for a period of 60 days. Effect of CS, on epididymis, adrenal weight, sperm count and sperm head shape abnormality was studied. 2 Epididymal weight remained unaltered in 25, 50 and 100 mg/kg CS2 treated groups, whereas in highest dose of CS2 treated (200 mg/kg) group a non-significant reduction in epididymis weight was observed. A slight increase in adrenal weight was observed in lower doses groups (25 and 50 mg/kg) while a considerable decrease in adrenal weight was noted in highest dose (200 mg/kg) of CS, treated group in the present study. 3 An increase in sperm head shape abnormality and decrease in sperm count was observed in all the CS2 treated groups. However, the changes were statistically significant only after higher dose of CS2 treatment as compared to control. 4 This study suggests that CS2 may have the potential to induce adverse effects on male reproductive system of rats. Sperm head shape abnormality assay used in this study also elicits germ cell genotoxic potential of carbon disulphide.
Multiple morphological abnormalities of the sperm flagella (MMAF) are the most severe form of asthenozoospermia due to impaired axoneme structure in sperm flagella. Dynein arms are necessary components of the sperm flagellar axoneme. In this study, we recruited 3 unrelated consanguineous Pakistani families with multiple MMAF-affected individuals, who had no overt ciliary symptoms. Whole-exome sequencing and Sanger sequencing identified 2 cilia and flagella associated protein 57 (
CFAP57
) loss-of-function mutations (c.2872C>T, p. R958*; and c.2737C>T, p. R913*) recessively segregating with male infertility. A mouse model mimicking the mutation (c.2872C>T) was generated and recapitulated the typical MMAF phenotype of
CFAP57
-mutated individuals. Both
CFAP57
mutations caused loss of the long transcript-encoded CFAP57 protein in spermatozoa from MMAF-affected individuals or from the
Cfap57
-mutant mouse model while the short transcript was not affected. Subsequent examinations of the spermatozoa from
Cfap57
-mutant mice revealed that CFAP57 deficiency disrupted the inner dynein arm (IDA) assembly in sperm flagella and that single-headed IDAs were more likely to be affected. Thus, our study identified 2 pathogenic mutations in
CFAP57
in MMAF-affected individuals and reported a conserved and pivotal role for the long transcript-encoded CFAP57 in IDAs’ assembly and male fertility.
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